This project utilizes a synapse between a large axon and an interneuron in the spinal cord of the lamprey to examine the role of Ca ions in transmitter release. For example, manipulation of the external Ca ions will permit the power function relating transmitter release to the external Ca ions concentration to be determined. Other experiments will explore the possibility that presynaptic depolarization, in addition to increasing Ca ions conductance, also alters the interaction between Ca ions and a site on the presynaptic membrane. To determine whether this Ca ions site is internal or external, cation ionophores will be used to move Ca ions into the fiber by means other than through the normal Ca ions channels. The cation ionophores will also be utilized to determine if the normal site of release of transmitter can be enhanced pharmacologically. Finally, a series of cations will be injected into the presynaptic fiber in the region of the synapse to study the antagonism between Ca ions and Mg ions. These iontophoresis experiments will also permit an analysis of whether internal Ca ions affect transmitter release through a kinetic or a screening action.